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https://www.readbyqxmd.com/read/28719094/discovery-and-characterization-of-a-novel-tryptophan-hydroxylase-1-inhibitor-as-a-prodrug
#1
Hailong Shi, Yaya Cui, Yifei Qin
Serotonin (5-HT) is an important neurotransmitter and paracrine signaling molecule in the gastrointestinal tract. Two distinct tryptophan hydroxylases (TPH), TPH1 and TPH2 are the rate-limiting enzymes in the 5-HT biosynthesis process. TPH1 expression is mainly limited in the enterochromaffin cells and distributed in peripheries such as the skin and gut, while TPH2 is the predominant isoform in the CNS. In this study, mol002291 was screened as a drug-like compound from the TCM database for the inhibitor of TPH...
July 18, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28718678/discovery-of-novel-isoflavone-derivatives-as-ache-buche-dual-targeted-inhibitors-synthesis-biological-evaluation-and-molecular-modelling
#2
Bo Feng, Xinpeng Li, Jie Xia, Song Wu
AChE and BuChE are druggable targets for the discovery of anti-Alzheimer's disease drugs, while dual-inhibition of these two targets seems to be more effective. In this study, we synthesised a series of novel isoflavone derivatives based on our hit compound G from in silico high-throughput screening and then tested their activities by in vitro AChE and BuChE bioassays. Most of the isoflavone derivatives displayed moderate inhibition against both AChE and BuChE. Among them, compound 16 was identified as a potent AChE/BuChE dual-targeted inhibitor (IC50: 4...
December 2017: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/28715864/in-vitro-and-in-vivo-anticancer-activity-of-2-acetyl-benzylamine-isolated-from-adhatoda-vasica-l-leaves
#3
C Balachandran, Y Arun, B Sangeetha, V Duraipandiyan, S Awale, N Emi, S Ignacimuthu, P T Perumal
One of the important aims of drug discovery for cancer is to find therapeutic agents from natural products that are effective and safe for cancer treatment. In the current study, an alkaloid, 2-acetyl-benzylamine, isolated from Adhatoda vasica, was screened for potent anticancer properties against leukemia cells. We used seven different types of leukemia cells such as CEM, NB-4, MOLM-14, Jurkat, IM-9, K562 and HL-60 for cytotoxic studies. 2-acetyl-benzylamine showed significant cytotoxic properties against MOLM-14 and NB-4 cells with IC50 values of 0...
July 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28713868/21st-century-cardio-oncology-identifying-cardiac-safety-signals-in-the-era-of-personalized-medicine
#4
Calvin Chen Sheng, Laleh Amiri-Kordestani, Todd Palmby, Thomas Force, Charles C Hong, Joseph C Wu, Kevin Croce, Geoffrey Kim, Javid Moslehi
Cardiotoxicity is a well-established complication of oncology therapies. Cardiomyopathy resulting from anthracyclines is a classic example. In the past decade, an explosion of novel cancer therapies, often targeted and more specific than traditional therapies, has revolutionized oncology therapy and dramatically changed cancer prognosis. However, some of these therapies have introduced an assortment of cardiovascular (CV) complications. At times, these devastating outcomes have only become apparent after drug approval and have limited the use of potent therapies...
August 2016: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28713765/prevalence-of-periodontal-pathogens-in-a-group-of-participants-from-the-middle-east-and-north-africa-geographic-region-with-minimal-periodontal-disease
#5
Zoubeida Al Yahfoufi, Wahib Hadchiti
AIM AND OBJECTIVES: To assess the prevalence of the three putative periodontal pathogens such as Aggregatibacter actinomycetemcomitans (A. a), Porphyromonas gingivalis (P. g), and Prevotella intermedia (P. i) in a group of Arab participants from the Middle East and North Africa (MENA) region who had minimal periodontal disease and no history of periodontal treatment and further to analyze the association among these three microorganisms. MATERIALS AND METHODS: Eighty-four participants of varied demographics and oral/dental care habits were screened for this study...
June 2017: Journal of International Society of Preventive & Community Dentistry
https://www.readbyqxmd.com/read/28713442/overdiagnosis-an-unrecognised-and-growing-worldwide-problem-in-healthcare
#6
EDITORIAL
John Brodersen
Overdiagnosis is the diagnosis of deviations, abnormalities, risk factors, and pathologies that in themselves would never cause symptoms (this applies only to risk factors and pathology), would never lead to morbidity, and would never be the cause of death. Therefore, treating an overdiagnosed condition (deviation, abnormality, risk factor, pathology) cannot, by definition, improve the patient's prognosis, and can therefore only be harmful. Overdiagnosis is an extremely harmful and big problem all over the world, and the problem is increasing...
September 2017: Zdravstveno Varstvo
https://www.readbyqxmd.com/read/28713441/analysis-of-raw-biofluids-by-mass-spectrometry-using-microfluidic-diffusion-based-separation
#7
Joshua Heinemann, Brigit Noon, Daniel Willems, Katherine Budeski, Brian Bothner
Elucidation and monitoring of biomarkers continues to expand because of their medical value and potential to reduce healthcare costs. For example, biomarkers are used extensively to track physiology associated with drug addiction, disease progression, aging, and industrial processes. While longitudinal analyses are of great value from a biological or healthcare perspective, the cost associated with replicate analyses is preventing the expansion of frequent routine testing. Frequent testing could deepen our understanding of disease emergence and aid adoption of personalized healthcare...
January 21, 2017: Analytical Methods: Advancing Methods and Applications
https://www.readbyqxmd.com/read/28713277/does-the-strategy-of-risk-group-testing-for-hepatitis-c-hit-the-target
#8
Mirjana R Jovanovic, Aleksandar Miljatovic, Laslo Puskas, Slobodan Kapor, Dijana L Puskas
In the European Union, it is estimated that there are 5.5 million individuals with chronic infection of hepatitis C. Intravenous drug abuse is undoubtedly the key source of the hepatitis C epidemic in Europe and the most efficient mode of transmission of HCV infections (primarily due to short incubation time, but also because the virus is introduced directly into the blood stream with the infected needle). Potentially high-risk and vulnerable populations in Europe (and the world) include immigrants, prisoners, sex workers, men having sex with men, individuals infected with HIV, psychoactive substance users etc...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28712979/clinical-implications-of-the-t790m-mutation-in-disease-characteristics-and-treatment-response-in-patients-with-epidermal-growth-factor-receptor-egfr-mutated-non-small-cell-lung-cancer%C3%A2-nsclc
#9
Daria Gaut, Myung Shin Sim, Yuguang Yue, Brian R Wolf, Phillip A Abarca, James M Carroll, Jonathan W Goldman, Edward B Garon
BACKGROUND: The secondary T790M mutation accounts for more than 50% of acquired tyrosine kinase inhibitor (TKI) resistance in patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Recent reports suggest this resistance mutation may be more common among patients with longer progression-free survival (PFS) on first-line TKI therapy, but much is still unknown. MATERIALS AND METHODS: Our group collected medical records from patients who underwent a biopsy for T790M mutation testing while screening for clinical trials involving the drug rociletinib (CO-1686), a T790M mutation-specific TKI...
June 20, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28710651/intoxication-caused-by-new-psychostimulants-analytical-methods-to-disclose-acute-and-chronic-use-of-benzofurans-and-ethylphenidate
#10
Bernardino Barceló, Isabel Gomila, Maria Concetta Rotolo, Emilia Marchei, Chrystalla Kyriakou, Simona Pichini, Carolina Roset, Miguel Ángel Elorza, Francesco Paolo Busardò
The acute and chronic toxicity of several new psychoactive substances (NPS) is unknown, and only little information is available on the pharmacology and toxicology, toxicokinetics, and detectability in body samples of such new compounds. We here propose analytical methods to disclose acute and chronic use of two types of new psychostimulants: benzofurans and ethylphenidate and we applied them to a real case of a subject attending Emergency Department with signs of acute intoxication due to psychotropic drug(s)...
July 15, 2017: International Journal of Legal Medicine
https://www.readbyqxmd.com/read/28710351/combination-therapy-for-tuberculosis-treatment-pulmonary-administration-of-ethionamide-and-booster-co-loaded-nanoparticles
#11
Joana Costa-Gouveia, Elisabetta Pancani, Samuel Jouny, Arnaud Machelart, Vincent Delorme, Giuseppina Salzano, Raffaella Iantomasi, Catherine Piveteau, Christophe J Queval, Ok-Ryul Song, Marion Flipo, Benoit Deprez, Jean-Paul Saint-André, José Hureaux, Laleh Majlessi, Nicolas Willand, Alain Baulard, Priscille Brodin, Ruxandra Gref
Tuberculosis (TB) is a leading infectious cause of death worldwide. The use of ethionamide (ETH), a main second line anti-TB drug, is hampered by its severe side effects. Recently discovered "booster" molecules strongly increase the ETH efficacy, opening new perspectives to improve the current clinical outcome of drug-resistant TB. To investigate the simultaneous delivery of ETH and its booster BDM41906 in the lungs, we co-encapsulated these compounds in biodegradable polymeric nanoparticles (NPs), overcoming the bottlenecks inherent to the strong tendency of ETH to crystallize and the limited water solubility of this Booster...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710214/trends-and-factors-in-human-immunodeficiency-virus-and-or-hepatitis-c-virus-testing-and-infection-among-injection-drug-users-newly-entering-methadone-maintenance-treatment-in-guangdong-province-china-2006-2013-a-consecutive-cross-sectional-study
#12
Yin Liu, Yu Liu, Xia Zou, Wen Chen, Li Ling
OBJECTIVES: To assess trends and related factors in HIV and/or hepatitis C virus (HCV) antibody testing and infection among injection drug users (IDUs) newly entering methadone maintenance treatment (MMT) in Guangdong Province, China. METHOD: Consecutive cross sectional surveys were conducted in 14 MMT clinics from July 2006 to December 2013 in Guangdong Province, China. IDUs were excluded if they were re-enrolled or referred from other MMT clinics. Trend tests were used to examine HIV and/or HCV testing and infection, sociodemographic characteristics, drug use related behaviours and the past 3 month sexual behaviours on enrolment...
July 13, 2017: BMJ Open
https://www.readbyqxmd.com/read/28710036/effect-of-polymorphisms-in-transporter-genes-on-dosing-efficacy-and-toxicity-of-maintenance-therapy-in-children-with-acute-lymphoblastic-leukemia
#13
Guillermo Gervasini, Silvia G de Murillo, Mercedes Jiménez, María D de la Maya, Jose M Vagace
The aim of the present work was to assess whether polymorphisms in genes coding for drug transport proteins may influence dosing, efficacy and toxicity of maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6MP) in childhood acute lymphoblastic leukemia (ALL). A total of 41 children with ALL were screened for 10 SNPs in the SLC19A1, ABCB1, ABCC2, ABCC4 and ABCG2 transporter genes by means of direct sequencing. Carriers of the ABCC4 934CC and ABCB1 1236TT genotypes received a lower percentage of the protocol-recommended starting dose of MTX (62...
July 11, 2017: Gene
https://www.readbyqxmd.com/read/28709952/potent-inhibitors-of-human-lat1-slc7a5-transporter-based-on-dithiazole-and-dithiazine-compounds-for-development-of-anticancer-drugs
#14
Lara Napolitano, Mariafrancesca Scalise, Maria Koyioni, Panayotis Koutentis, Marco Catto, Ivano Eberini, Chiara Parravicini, Luca Palazzolo, Leonardo Pisani, Michele Galluccio, Lara Console, Angelo Carotti, Cesare Indiveri
The LAT1 transporter is acknowledged as a pharmacological target of tumours since it is strongly overexpressed in many human cancers. The purpose of this work was to find novel compounds exhibiting potent and prolonged inhibition of the transporter. To this aim, compounds based on dithiazole and dithiazine scaffold have been screened in the proteoliposome experimental model. Inhibition was tested on the antiport catalysed by hLAT1 as transport of extraliposomal [(3)H]histidine in exchange with intraliposomal histidine...
July 11, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28708696/prevalence-of-human-immunodeficiency-virus-and-sexually-transmitted-infections-among-cisgender-and-transgender-women-sex-workers-in-greater-kuala-lumpur-malaysia-results-from-a-respondent-driven-sampling-study
#15
Jeffrey A Wickersham, Britton A Gibson, Alexander R Bazazi, Veena Pillai, Courtney J Pedersen, Jaimie P Meyer, Nabila El-Bassel, Kenneth H Mayer, Adeeba Kamarulzaman, Frederick L Altice
BACKGROUND: Sex workers face a disproportionate burden of human immunodeficiency virus (HIV) and sexually transmitted infections (STI) worldwide. For cisgender women sex workers (CWSW), global HIV prevalence is over 10%, whereas transgender women sex workers (TWSW) face an HIV burden of 19% to 27%. METHODS: We used respondent-driven sampling to recruit 492 sex workers, including CWSW (n = 299) and TWSW (n = 193) in Greater Kuala Lumpur, Malaysia. Participants completed an in-depth survey and were screened for HIV, syphilis, Chlamydia trachomatis, and Neisseria gonorrhoeae...
June 20, 2017: Sexually Transmitted Diseases
https://www.readbyqxmd.com/read/28707597/detection-of-extended-spectrum-beta-lactamases-esbls-and-antibiotic-susceptibility-patterns-in-klebsiella-pneumoniae-in-western-iran
#16
Pegah Shakib, Rashid Ramazan Zadeh, Morovat Taherikalani, Bijan Nouri
BACKGROUND: Production of Beta-Lactamase enzymes, especially extended-spectrum Beta -Lactamases (ESBL), is a primary mechanism of resistance in these bacteria. The purpose of this study was detection of blaTEM, blaSHV, blaCTX-M, blaCTX-M-15, blaPER and blaVEB in K. pneumoniae, isolated from clinical specimens by the PCR method and antibiotic susceptibility patterns in these strains isolated, in Sanandaj city, Iran. MATERIALS AND METHODS: During a period from October 2015 to July 2016, 52 K...
July 13, 2017: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/28707581/synthesis-and-evaluation-of-novel-diazaspiro-hydantoins-as-potential-anticonvulsants
#17
C S Ananda Kumar, B Veeresh, K C Ramesha, C S Ashok Raj, K M Mahadevaiah, S B Benaka Prasad
A series of novel diazaspiro compounds 6a-t were synthesised and biologically evaluated for their anticonvulsant activity in the maximal electroshock seizure (MES) assay. Most of the tested compounds exhibited moderate to weak activity in the MES screen test, The compounds 6f, 6h, 6i, 6j, 6p, 6s and 6n able to protect seizure effect significantly higher and this effect was similar when compared to standard drug treated rats.
July 12, 2017: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28707282/a-system-to-identify-inhibitors-of-mtor-signaling-using-high-resolution-growth-analysis-in-saccharomyces-cerevisiae
#18
Mitchell B Lee, Daniel T Carr, Michael G Kiflezghi, Yan Ting Zhao, Deborah B Kim, Socheata Thon, Margarete D Moore, Mary Ann K Li, Matt Kaeberlein
The mechanistic target of rapamycin (mTOR) is a central regulator of growth and proliferation and mTOR inhibition is a promising therapy for a variety of diseases and disorders. Inhibition of mTOR complex I (mTORC1) with rapamycin delays aging and increases healthy longevity in laboratory animals and is used clinically at high doses to prevent organ transplant rejection and to treat some forms of cancer. Clinical use of rapamycin is associated with several unwanted side effects, however, and several strategies are being taken to identify mTORC1 inhibitors with fewer side effects...
July 13, 2017: GeroScience
https://www.readbyqxmd.com/read/28706384/antimicrobial-susceptibility-risk-factors-and-prevalence-of-bla-cefotaximase-temoneira-and-sulfhydryl-variable-genes-among-escherichia-coli-in-community-acquired-pediatric-urinary-tract-infection
#19
Kallyadan V Nisha, Shetty A Veena, Shenoy D Rathika, Shenoy M Vijaya, Shetty K Avinash
INTRODUCTION: The emergence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has become an important challenge among pediatric patients with community-acquired urinary tract infection (UTI). OBJECTIVES: The aim of this study was to assess the antimicrobial susceptibility patterns, associated risk factors and to survey the frequency of bla cefotaximase (CTX-M), bla temoneira (TEM), and bla sulfhydryl variable (SHV) genotypes in ESBL-producing E...
July 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28706157/a-bayesian-pick-the-winner-design-in-a-randomized-phase-ii-clinical-trial
#20
Dung-Tsa Chen, Po-Yu Huang, Hui-Yi Lin, Alberto A Chiappori, Dmitry I Gabrilovich, Eric B Haura, Scott J Antonia, Jhanelle E Gray
PURPOSE: Many phase II clinical trials evaluate unique experimental drugs/combinations through multi-arm design to expedite the screening process (early termination of ineffective drugs) and to identify the most effective drug (pick the winner) to warrant a phase III trial. Various statistical approaches have been developed for the pick-the-winner design but have been criticized for lack of objective comparison among the drug agents. METHODS: We developed a Bayesian pick-the-winner design by integrating a Bayesian posterior probability with Simon two-stage design in a randomized two-arm clinical trial...
July 7, 2017: Oncotarget
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